Ric‐8: Different cellular roles for a heterotrimeric G‐protein GEF

Hinrichs, María Victoria; Torrejón, Marcela; Montecino, Martín; Olate, Juan

doi:10.1002/jcb.24162

Cited by 28 publications

(34 citation statements)

References 65 publications

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“…If RicA is an ortholog of Ric-8 in animals, it likely functions in activation of heterotrimeric G protein signaling (24). As RicA is clearly needed for growth and development, we carried out a series of doublemutant analyses to examine the genetic interactions of RicA with other key regulators in A. nidulans.…”

Section: Resultsmentioning

confidence: 99%

“…The RIC-8 orthologs are present in genomes of animals and filamentous fungi, but not in baker's yeast or plants. Whereas the C. elegans and Drosophila genomes contain a single Ric-8 gene, mammals possess two Ric-8 orthologs, Ric-8A and Ric-8B (24). Unlike GPCRs, Ric-8 proteins cannot stimulate the guanine nucleotide exchange activity of the G␣ subunit associated with G␤␥, i.e., the inactive heterotrimeric complex.…”

Section: Discussionmentioning

confidence: 99%

“…Thus, Ric-8 proteins can only function on dissociated (free) monomeric G␣-GDP (Fig. 1A) (24,60). It has been hypothesized that RIC-8 was acquired by animals and certain fungi after G proteins and GPCRs evolved and is therefore a fairly recent addition to G protein regulatory pathways (65).…”

Section: Discussionmentioning

confidence: 99%

“…One key element facilitating inactivation is the regulator of G protein signaling (RGS), which accelerates GTP hydrolysis catalyzed by the G␣ subunit (15). While GPCR-mediated signaling accounts for the majority of G proteinregulated cellular control mechanisms, the evolutionarily conserved RIC-8 (resistance to inhibitors of cholinesterase 8) protein is a proven critical guanine nucleotide exchange factor (GEF) that activates a subset of G␣ subunits (24). Ric-8 interacts with monomeric G␣-GDP, stimulates the release of GDP, forms a stable nucleotide-free transition-state complex with the G␣ subunit, and catalyzes the exchange of GDP for GTP (Fig.…”

mentioning

confidence: 99%

“…Ric-8 interacts with monomeric G␣-GDP, stimulates the release of GDP, forms a stable nucleotide-free transition-state complex with the G␣ subunit, and catalyzes the exchange of GDP for GTP (Fig. 1A) (5,24).…”

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confidence: 99%

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The Putative Guanine Nucleotide Exchange Factor RicA Mediates Upstream Signaling for Growth and Development in Aspergillus

et al. 2012

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dHeterotrimeric G proteins (G proteins) govern growth, development, and secondary metabolism in various fungi. Here, we characterized ricA, which encodes a putative GDP/GTP exchange factor for G proteins in the model fungus Aspergillus nidulans and the opportunistic human pathogen Aspergillus fumigatus. In both species, ricA mRNA accumulates during vegetative growth and early developmental phases, but it is not present in spores. The deletion of ricA results in severely impaired colony growth and the total (for A. nidulans) or near (for A. fumigatus) absence of asexual sporulation (conidiation). The overexpression (OE) of the A. fumigatus ricA gene (AfricA) restores growth and conidiation in the ⌬AnricA mutant to some extent, indicating partial conservation of RicA function in Aspergillus. A series of double mutant analyses revealed that the removal of RgsA (an RGS protein of the GanB G␣ subunit), but not sfgA, flbA, rgsB, or rgsC, restored vegetative growth and conidiation in ⌬AnricA. Furthermore, we found that RicA can physically interact with GanB in yeast and in vitro. Moreover, the presence of two copies or OE of pkaA suppresses the profound defects caused by ⌬AnricA, indicating that RicA-mediated growth and developmental signaling is primarily through GanB and PkaA in A. nidulans. Despite the lack of conidiation, brlA and vosA mRNAs accumulated to normal levels in the ⌬ricA mutant. In addition, mutants overexpressing fluG or brlA (OEfluG or OEbrlA) failed to restore development in the ⌬AnricA mutant. These findings suggest that the commencement of asexual development requires unknown RicA-mediated signaling input in A. nidulans.

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Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

mentioning

confidence: 99%

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The Putative Guanine Nucleotide Exchange Factor RicA Mediates Upstream Signaling for Growth and Development in Aspergillus

et al. 2012

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Targeted deletion of RIC8A in mouse neural precursor cells interferes with the development of the brain, eyes, and muscles

Kask

Tikker

Ruisu

et al. 2018

Developmental Neurobiology

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Autosomal recessive disorders such as Fukuyama congenital muscular dystrophy, Walker-Warburg syndrome, and the muscle-eye-brain disease are characterized by defects in the development of patient's brain, eyes, and skeletal muscles. These syndromes are accompanied by brain malformations like type II lissencephaly in the cerebral cortex with characteristic overmigrations of neurons through the breaches of the pial basement membrane. The signaling pathways activated by laminin receptors, dystroglycan and integrins, control the integrity of the basement membrane, and their malfunctioning may underlie the pathologies found in the rise of defects reminiscent of these syndromes. Similar defects in corticogenesis and neuromuscular disorders were found in mice when RIC8A was specifically removed from neural precursor cells. RIC8A regulates a subset of G-protein α subunits and in several model organisms, it has been reported to participate in the control of cell division, signaling, and migration. Here, we studied the role of RIC8A in the development of the brain, muscles, and eyes of the neural precursor-specific conditional Ric8a knockout mice. The absence of RIC8A severely affected the attachment and positioning of radial glial processes, Cajal-Retzius' cells, and the arachnoid trabeculae, and these mice displayed additional defects in the lens, skeletal muscles, and heart development. All the discovered defects might be linked to aberrancies in cell adhesion and migration, suggesting that RIC8A has a crucial role in the regulation of cell-extracellular matrix interactions and that its removal leads to the phenotype characteristic to type II lissencephaly-associated diseases. © 2018 Wiley Periodicals, Inc. Develop Neurobiol 78: 374-390, 2018.

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The CREB Transcription Factor Controls Transcriptional Activity of the Human RIC8B Gene

Maureira

Sánchez

Valenzuela

et al. 2016

J of Cellular Biochemistry

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Proper regulation of gene expression is essential for normal development, cellular growth, and differentiation. Differential expression profiles of mRNA coding for vertebrate Ric-8B during embryo and adult stages have been observed. In addition, Ric-8B is expressed in few cerebral nuclei subareas. These facts point to a dynamic control of RIC8B gene expression. In order to understand the transcriptional regulation of this gene, we searched for cis-elements in the sequence of the human RIC8B promoter region, identifying binding sites for the basic/leucine zipper (bZip) CREB transcription factor family (CRE sites) and C/EBP transcription factor family (C/EBP sites). CRE sites were found clustered near the transcription start site, while the C/EBP sites were found clustered at around 300 bp upstream the CRE sites. Here, we demonstrate the ability of CREB1 and C/EBPβ to bind their respective elements identified in the RIC8B promoter. Comparative protein-DNA interaction analyses revealed only the proximal elements as high affinity sites for CREB1 and only the distal elements as high affinity sites for C/EBPβ. Chromatin immunoprecipitation analyses, carried out using a human neuroblastoma cell line, confirmed the preferential association of CREB to the proximal region of the RIC8B promoter. By performing luciferase reporter assays, we found the CRE sites as the most relevant elements for its transcriptional activity. Taken together, these data show the existence of functional CREB and C/EBP binding sites in the human RIC8B gene promoter, a particular distribution of these sites and demonstrate a relevant role of CREB in stimulating transcriptional activity of this gene. J. Cell. Biochem. 117: 1797-1805, 2016. © 2016 Wiley Periodicals, Inc.

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Ric‐8: Different cellular roles for a heterotrimeric G‐protein GEF

Cited by 28 publications

References 65 publications

The Putative Guanine Nucleotide Exchange Factor RicA Mediates Upstream Signaling for Growth and Development in Aspergillus

The Putative Guanine Nucleotide Exchange Factor RicA Mediates Upstream Signaling for Growth and Development in Aspergillus

Targeted deletion of RIC8A in mouse neural precursor cells interferes with the development of the brain, eyes, and muscles

The CREB Transcription Factor Controls Transcriptional Activity of the Human RIC8B Gene

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